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   Summary: Transplanting fecal microbiota from young mice to older mice   
   reversed hallmark signs of aging in the gut, brains, and eyes.   
   Transplanting the fecal microbiota from old to young mice had the reverse   
   effect, inducing inflammation in the brain and depleting a key protein   
   associated with healthy vision.   
      
   Source: University of East Anglia   
      
   In the search for eternal youth, poo transplants may seem like an unlikely   
   way to reverse the aging process.   
      
   However, scientists at the Quadram Institute and the University of East   
   Anglia have provided evidence, from research in mice, that transplanting   
   fecal microbiota from young into old mice can reverse hallmarks of aging   
   in the gut, eyes, and brain.   
      
   In the reverse experiment, microbes from aged mice induced inflammation in   
   the brain of young recipients and depleted a key protein required for   
   normal vision.   
      
   These findings show that gut microbes play a role in the regulating some   
   of the detrimental effects of aging and open up the possibility of gut   
   microbe-based therapies to combat decline in later life.   
      
   Prof Simon Carding, from UEA’s Norwich Medical School and head of the Gut   
   Microbes and Health Research Program at the Quadram Institute, said: “This   
   ground-breaking study provides tantalizing evidence for the direct   
   involvement of gut microbes in aging and the functional decline of brain   
   function and vision and offers a potential solution in the form of gut   
   microbe replacement therapy.”   
      
   It has been known for some time that the population of microbes that we   
   carry around in our gut, collectively called the gut microbiota, is linked   
   to health. Most diseases are associated with changes in the types and   
   behavior of bacteria, viruses, fungi and other microbes in an individual’s   
   gut.   
      
   Some of these changes in microbiota composition happen as we age,   
   adversely affecting metabolism and immunity, and this has been associated   
   with age-related disorders including inflammatory bowel diseases, along   
   with cardiovascular, autoimmune, metabolic and neurodegenerative   
   disorders.   
      
   To better understand the effects of these changes in the microbiota in old   
   age, scientists from the Quadram Institute transferred the gut microbes   
   from aged mice into healthy young mice, and vice versa. They then looked   
   at how this affected inflammatory hallmarks of aging in the gut, brain and   
   eye, which suffer from declining function in later life.   
      
   The study, published in the journal Microbiome, found that the microbiota   
   from old donors led to loss of integrity of the lining of the gut,   
   allowing bacterial products to cross into the circulation, which results   
   in triggering the immune system and inflammation in the brain and eyes.   
      
   Age-related chronic inflammation, known as inflammaging, has been   
   associated with the activation of specific immune cells found in brain.   
   These cells were also over-activated in the young mice who received aged   
   microbiome transplants.   
      
   In the eye, the team also found specific proteins associated with retinal   
   degeneration were elevated in the young mice receiving microbiota from old   
   donors.   
      
   In old mice, these detrimental changes in the gut, eye and brain could be   
   reversed by transplanting the gut microbiota from young mice.   
      
   In ongoing studies, the team are now working to understand how long these   
   positive effects can last, and to identify the beneficial components of   
   the young donor microbiota and how they impact on organs distant from the   
   gut.   
      
   The microbiota of young mice, and the old mice who received young   
   microbiota transplants were enriched in beneficial bacteria that have   
   previously been associated with good health in both mice and humans.   
      
   The researchers have also analyzed the products which these bacteria   
   produce by breaking down elements of our diet. This has uncovered   
   significant shifts in particular lipids (fats) and vitamin metabolism,   
   which may be linked to the changes seen in inflammatory cells in the eye   
   and brain.   
      
   Similar pathways exist in humans, and the human gut microbiota also   
   changes significantly in later life, but the researchers caution about   
   extrapolating their results directly to humans until similar studies in   
   elderly humans can be performed.   
      
   A new facility for Microbiota Replacement Therapy (MRT), also known as   
   Fecal Microbiota Transplantation (FMT) is being built in the Quadram   
   Institute that will facilitate such trials, as well as other trials for   
   microbiota-related conditions.   
      
   Lead author of the study, Dr. Aimee Parker from the Quadram Institute   
   said: “We were excited to find that by changing the gut microbiota of   
   elderly individuals, we could rescue indicators of age-associated decline   
   commonly seen in degenerative conditions of the eye and brain.   
      
   “Our results provide more evidence of the important links between microbes   
   in the gut and healthy aging of tissues and organs around the body. We   
   hope that our findings will contribute ultimately to understanding how we   
   can manipulate our diet and our gut bacteria to maximize good health in   
   later life.”   
      
   About this microbiome and aging research news   
   Author: Press Office   
   Source: University of East Anglia   
   Contact: Press Office – University of East Anglia   
   Image: The image is in the public domain   
      
   Original Research: Closed access.   
   “Fecal microbiota transfer between young and aged mice reverses hallmarks   
   of the aging gut, eye, and brain” by Aimée Parker et al. Microbiome   
      
   Abstract   
      
   Fecal microbiota transfer between young and aged mice reverses hallmarks   
   of the aging gut, eye, and brain   
      
   Background   
   Altered intestinal microbiota composition in later life is associated with   
   inflammaging, declining tissue function, and increased susceptibility to   
   age-associated chronic diseases, including neurodegenerative dementias.   
   Here, we tested the hypothesis that manipulating the intestinal microbiota   
   influences the development of major comorbidities associated with aging   
   and, in particular, inflammation affecting the brain and retina.   
      
   Methods   
   Using fecal microbiota transplantation, we exchanged the intestinal   
   microbiota of young (3 months), old (18 months), and aged (24 months)   
   mice. Whole metagenomic shotgun sequencing and metabolomics were used to   
   develop a custom analysis workflow, to analyze the changes in gut   
   microbiota composition and metabolic potential. Effects of age and   
   microbiota transfer on the gut barrier, retina, and brain were assessed   
   using protein assays, immunohistology, and behavioral testing.   
      
   Results   
   We show that microbiota composition profiles and key species enriched in   
   young or aged mice are successfully transferred by FMT between young and   
   aged mice and that FMT modulates resulting metabolic pathway profiles. The   
   transfer of aged donor microbiota into young mice accelerates age-   
   associated central nervous system (CNS) inflammation, retinal   
      
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